Associations among executive function Abilities, free Water, and white matter microstructure in early old age

Daniel E. Gustavson; Derek B. Archer; Jeremy A. Elman; Olivia K. Puckett; Christine Fennema-Notestine; Matthew S. Panizzon; Niranjana Shashikumar; Timothy J. Hohman; Angela L. Jefferson; Lisa T. Eyler; Linda K. McEvoy; Michael J. Lyons; Carol E. Franz; William S. Kremen

NeuroImage: Clinical (Jan 2023)

Associations among executive function Abilities, free Water, and white matter microstructure in early old age

Daniel E. Gustavson,
Derek B. Archer,
Jeremy A. Elman,
Olivia K. Puckett,
Christine Fennema-Notestine,
Matthew S. Panizzon,
Niranjana Shashikumar,
Timothy J. Hohman,
Angela L. Jefferson,
Lisa T. Eyler,
Linda K. McEvoy,
Michael J. Lyons,
Carol E. Franz,
William S. Kremen

Affiliations

Daniel E. Gustavson: Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding author at: Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Derek B. Archer: Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, USA
Jeremy A. Elman: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA
Olivia K. Puckett: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA
Christine Fennema-Notestine: Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA; Department of Radiology, University of California San Diego, La Jolla, CA, USA
Matthew S. Panizzon: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA
Niranjana Shashikumar: Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, USA
Timothy J. Hohman: Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, USA
Angela L. Jefferson: Vanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, USA
Lisa T. Eyler: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA
Linda K. McEvoy: Department of Radiology, University of California San Diego, La Jolla, CA, USA; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA
Michael J. Lyons: Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
Carol E. Franz: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA
William S. Kremen: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA

Journal volume & issue: Vol. 37
p. 103279

Abstract

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Background: Studies have investigated white matter microstructure in relation to late-life cognitive impairments, with fractional anisotropy (FA) and mean diffusivity (MD) measures thought to capture demyelination and axonal degradation. However, new post-processing methods allow isolation of free water (FW), which captures extracellular fluid contributions such as atrophy and neuroinflammation, from tissue components. FW also appears to be highly relevant to late-life cognitive impairment. Here, we evaluated whether executive functions are associated with FW, and FA and MD corrected for FW (FAFWcorr and MDFWcorr). Method: We examined 489 non-demented men in the Vietnam Era Twin Study of Aging (VETSA) at mean age 68. Two latent factors capturing ‘common executive function’ and ‘working-memory specific’ processes were estimated based on 6 tasks. Analyses focused on 11 cortical white matter tracts across three metrics: FW, FAFWcorr, and MDFWcorr. Results: Better ‘common executive function’ was associated with lower FW across 9 of the 11 tracts. There were no significant associations with intracellular metrics after false discovery rate correction. Effects also appeared driven by individuals with MCI (13.7% of the sample). Working memory-specific tasks showed some associations with FAFWcorr, including the triangularis portion of the inferior frontal gyrus. There was no evidence that cognitive reserve (i.e., general cognitive ability assessed in early adulthood) moderated these associations between executive function and FW or FA. Discussion: Executive function abilities in early old age are associated primarily with extracellular fluid (FW) as opposed to white matter (FAFWcorr or MDFWcorr). Moderation analyses suggested cognitive reserve does not play a strong role in these associations, at least in this sample of non-demented men.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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